5h - 3,4,6,7 - tetrahydro-10 - methoxy-5-methyl-6- (1',1'- dioxido-3'- meta - chloraniline-4'- methoxy - benzo [b] thiophene -7'-yl) -furo[4,3,2-q] benzazocin with an antidepressant
(57) Abstract:Usage: as antidepressant funds. The inventive product-5H-3,4,6,7-tetrahydro-10-methoxy-5-methyl-6 - 11-dioxido - 3-meta-X-laranjinha - 4-methoxybenzo[B]thiophene - 7-yl)furo[4,3,2 - Q] benzazocin. BF C29H27ClN2O5S , yield 77%, so pl. 152-156°C. table 4. The invention relates to new chemical compound, specifically to 5H-3,4,6,7-tetrahydro-10-methoxy-5-methyl-6-(1', 1'-dioxide)-3'- metalorigin-4'-methoxy-benzo[B] thiophene-7 yl)-furo-[4.3.2. -Q] -benzazocine, formula I
with an antidepressant.The specified connection and its properties are not described in literature.Despite the presence of a large group of substances that have a stimulating effect on the Central nervous system of patients suffering from depression, finding new compounds that have a positive impact on the emotional state of patients is important. This is due to the slow development of therapeutic effect of known antidepressants (12-5) days from the beginning of the application, holinoblokirutm activity of several drugs (amitriptyline, imizine, maprotiline), incompatibility with other groups of drug competitiveness to silvanio hypertensive actions of biogenic sosudosuzhivayuschih monoamines (tiramina, of phenethylamine) .Similar in structure to the claimed compounds is galantamine (nivalin) is a reversible cholinesterase inhibitor , formulas
< / BR>Also known 7,8- -diolan-4-he-S,S-dioxido)-6,14-endoetheno-tetrahydrofuran, formulas
the predecessor of the claimed compounds with analgesic activity .Analogous to the properties of the claimed compounds is amitriptyline, formulas
having antidepressant activity.The aim of the invention is the search for new derivatives benzazocine having a stimulating effect on the Central nervous system and have advantages over the known analogues. This goal was achieved new benzo trefentanil framentation the formula I with an antidepressant. The method of obtaining the proposed connection is condensation  10-methoxy-6-(4'-methoxy 1',1',3'-trioxo-2', 3'-dihydro - benzothiazol-7')-5-methyl-3,4,6,7 - tetrahydro-5H-furo[4.3.2-Q]benzazocine with 3-Chloroaniline by boiling in acetic acid for 3 hours, the Yield of substance I is 77%.< / BR>Acute toxicity and antidepressant effects of compound I has been studied in the laboratory new is knosti of the studied compounds and the most widely used in medical practice antidepressants.From the data table.1 shows that compound I is 2-4 times less toxic than used in medical practice antidepressants. The substance I belongs to the 3rd class of mild-hazard substances.The antidepressant activity of the proposed compounds were studied in outbred mice weighing 16-18 g On the effects of the compounds on the Central nervous system to be judged by the change in the estimated reactions, duration of sleeping pills, apomorfina and fenaminovoj stereotypia, time of immobilization, the effect on emotional status and aggressiveness.The investigated compound was administered orally in a dose of 5.0 mg/kg Antidepressant effect of a substance compared with the effect of amitriptyline, introduced at a dose of 10.0 mg/kg, and imizine (melipramin), introduced at a dose of 10.0 mg/kg of the test Results are given in table.2-4.From the data table. 2 shows that the connection I increases the estimated response at the dose of 5.0 mg/kg test "hit the wall" physical activity increases 3 times, 2.5 times the number of surveyed holes compared with the control group. The connection I increases the locomotor activity of the animals compared to the concentration activity of the BL.3 shows data on the impact of the new framentation on the duration of the hypnotic effect of barbiturates (chloral hydrate and geksenala) and on the duration fenaminovoj and apomorfina stereotypie.From the data table.3 shows that the studied compound potentional effect sleeping pills - geksenala 1.3 times, chloral hydrate - 2.2 times, which indicates that he has a sedative effect. The effect of compounds introduced at a dose of 5.0 mg/kg (1/200 from LD50similar effect amitriptyline entered in the dose of 10 mg/kg (1/30 from LD50).Benzothiazepines framentation (I) blocks the effects of amphetamine and apomorphine in contrast to antidepressants of melipramin and amitriptyline, which have a negligible effect on serotonin receptors.In table. 4 shows the effect of compound I on the emotional status of the animal, aggressiveness, defined by the method of provocation and electrovalves irritation  , and according to the time change immobilization test "hanging by the tail" .From the data table.4 shows that the studied compound I does not change the emotional status of animals in comparison with control and known antidepressants. Introduction compounds at a dose of 5.0 mg/kg leads to an increase in time of immobilization 1.2 times compared with the control group and similar to amitriptyline entered in a dose twice as much, which can be attributed timolepticheskoe effect Isle high voltage, defiant response to the summary than in animals of the control group. Anti-anxiety activity of compound I in this model is similar to amitriptyline.Thus, 5H-3,4,6,7-tetrahydro-10-methoxy-5-methyl-6-(1',1'-dioxido-3'-meta - chloraniline-4'-methoxy-benzo[b]thiophene-7'-yl)-furo[4,3,2-Q] benzazocin connection moderately toxic, the range of actions on the Central nervous system has a pronounced anti-depressive effect, accompanied by strong sedative effect similar to aminotrimethylene. The proposed connection is active at a dose 4 times less LD50in comparison with the known antidepressants.P R I m e R 1. Synthesis of 5H-3,4,6,7-tetrahydro-10-methoxy-5-methyl-6-(1', 1'-dioxido - 3'-meta - chloraniline-4'-methoxy-benzo[b] thiophene-7'-yl)-furo[4,3,2-Q] benzazocine (1). To a solution of 0.44 g (0.001 mol) of 10-methoxy-6-(4'-methoxy-1', 1', 3 trioxo-2,3-dihydrobenzo[b] thienyl - 7')-5-methyl-3,4,6,7-tetrahydro-5H-furo[4,3,2-Q]Ben-tazocin in 30 ml of acetic acid was added 0.14 g (0,0012 mol) of m-Chloroaniline and the reaction mass was heated 3 hours the Solution was boiled away on the Petri dish, the residue was led from ethyl acetate, got 0,42 g (77%) of substance (I). So pl. 152-156aboutC.IR spectrum (cm-1) - 1020, 1060, 1110, 1210, ), 3,93, 3,98 C (CH3), 6,70 d (2N,N8,9), 7.00 m (6N,N2,4,H-Ar), 7,33 D. D. (2N,N5,6), of 7.82 (1H,H2).Found,%: C 63,6; H 5,2; N 4,9; Cl 6,6; S 6,0.C29H27ClN2O5S.Calculated,%: C 63,2; H Is 4.9; N 5,1; Cl 6,4; S 5,8.P R I m m e R 2. The impact of the proposed connection on the estimated reaction was studied on 28 animals in terms intraperitoneal administration. The target compound was administered at a dose of 5.0 mg/kg; the activity of the compounds was compared with the effect melipramin and amitriptyline entered in doses of 10.0 mg/kg With the introduction of the described compounds locomotor activity of animals significantly increases. The number of surveyed holes on the horizontal test is 28,0, in the control group of 11.1. The number of vertical stevani with the introduction of a substance (I) is 15.6, in the control group - 5,5, within 1 min.P R I m e R 3. The effect of compound I on the hypnotics drugs studied 56 animals. Geksenal or chloral hydrate was administered orally in doses of 75.0 or 300,0 mg/kg of the Studied compound was administered at a dose of 5.0 mg/kg Duration chloralhydrate sleep with the introduction of compound I is 192 min in the control group of 87 minutes Duration geksenalovy sleep with animovie and dopamine receptors studied by changing the length fenaminovoj and apomorfina stereotypie. Studies were performed on 48 animals. Apomorphine was administered at a dose of 20 mg/kg amphetamine 10 mg/kg subcutaneously every hour after administration of the substance I in a dose of 5.0 mg/kg Study the connection blocks the effects of amphetamine and apomorphine. Duration fenaminovoj stereotypie is 88 minutes, in control - 124 min, apomorphine - 58 min in the control group (60 minP R I m e R 5. The impact of the proposed connection on the emotional status was assessed by the level of stress during capture of the animal by hand (on a 3-point scale). The amount of emotional stress when introducing the compound at a dose of 5.0 mg/kg was 1.0 score in the control group - 0.96 points.P R I m e R 6. The impact of the proposed connection to the aggressiveness of the animals studied by the method of provocation - electrobalance irritation when passing a pulsed electric current through the electrode the floor of the chamber with animals (2) . As considered the first signs of reaction of animals to irritation. With the introduction of compound I animals showed signs of aggression when the voltage 103, whereas in the control group this value is 57 Century.P R I m e R 7. The effect of the inventive compounds on animal immobilization isovelocity the immobilization time up to 235 min, in the control group - 129 minutes 5H-3,4,6,7-tetrahydro - 10-methoxy-5-methyl-6-(1', 1'-dioxido-3'-meta-chloraniline-4'-methoxy-benzo [b]thiophene-7'-yl)-furo-[4,3,2-Q] benzazocin formula
< / BR>with an antidepressant.
(I) with an antidepressant
FIELD: organic synthesis.
SUBSTANCE: invention provides compounds of general formula I:
, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.
EFFECT: increased choice of cysteine protease inhibitors.
34 cl, 1 tbl, 13 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to a new compound of the general formula (2) and a method for its preparing wherein R1 represents hydrogen atom or salt-forming metal; R2 represent a direct or branched (C1-C7)-halogenalkyl group; m represents a whole number from 2 to 14; n represents a whole number from 2 to 7; A represents a group taken among the following formulae: (3) , (4) ,
(17) , (18) , (19) , (20) , (23) , (25) and (26) wherein R3 in formula (6) represents a direct or branched group (C1-C5)-alkyl group; R8 in formulae (18) and (20) represents a direct or branched (C1-C5)-alkyl group, a direct or branched (C2-C5)-alkenyl group or a direct or branched (C2-C5)-alkynyl group; in formula (23) each R21, R22, R23 and R24 represents independently hydrogen atom, a direct or branched (C1-C5)-alkyl group, a direct or branched (C1-C7)-halogenalkyl group, halogen atom or acyl group; in formulae (25) and (26) X represents halogen atom; or enantiomers of compound, or hydrates, or pharmaceutically acceptable salts of compound, or its enantiomers. Also, invention relates to a pharmaceutical composition containing indicated compound as an active component and to a therapeutic agent used against breast cancer based on thereof.
EFFECT: valuable medicinal properties of compounds.
10 cl, 2 tbl, 39 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to new biphenylsulfonylcyanamides of the formula (I): wherein R1 means: 1. (C1-C8)-alkyl; 4. -CnH2n-nn-Y wherein nn = 0 or 2 and n = 0-4, and n is not 0 or 1 if nn = 2; 5. CnH2n-nn-Y wherein nn = 0 or 2 and n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with amino-group or NR(22)R(23); R2 means: 2. (C1-C)-alkyl; 4. (C2-C12)-alkenyl; 5. (C2-C8)-alkynyl; 6. -CnH2n-nn-Z wherein nn = 0 or 2; n = 0-4, and n is not or 1 if nn = 2; 7. -CnH2n-nn-Z wherein nn = 0 or 2; n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with a residue taken among a series: 1. phenyl; 3. NR(22)R(23); 5. COOR(16); R3 and R4 mean hydrogen atom; R5, R6 and R7 mean independently of one another hydrogen atom (H), (C1-C8)-alkyl; SO2-(C1-C4)-alkyl, F, Cl, Br, J, OR(10) wherein R(10) means hydrogen atom, (C1-C4)-alkyl that is substituted if necessary with methoxy- or ethoxy-group; R(9) means OR(13) wherein R(13) means hydrogen atom, H,(C1-C8)-alkyl;X means carbonyl group, -CO-CO- or sulfonyl group; Y and Z mean independently of one another: 1. phenyl, 1-naphthyl, 2-naphthyl; 2. one of residues determined in cl. 1 substituted with 1-5 similar or different residues taken among a series: phenyl, F, Cl, Br, J, CF3, SOqR(18), OR(16), NR(19)R(20), -CN, NO2, COR(9), or two residues form methylenedioxy-group; 3. furyl, thienyl, pyridyl, benzimidazolyl, indolyl, benzothiophenyl, dihydroquinazolinyl; 5. (C3-C10)-cycloalkyl wherein cyclopropyl, cyclopentyl, cyclohexyl and indalyl are preferable; 6. one of residues determined in cl. 5 substituted with phenyl; R(16) means: 1. hydrogen atom; 2. (C1-C4)-alkyl; 3. (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; R(19) and R(20) mean independently: hydrogen atom (H), (C1-C4)-alkyl; R(22) and R(23) mean independently of one another hydrogen atom (H) or CO-OR(24) wherein R924) means -CnH2n-phenyl wherein n = 1-4; q = 2; and their physiologically acceptable salts. Compound of the formula (I) inhibit sodium-dependent chloride-bicarbonate exchange "NCBE".
EFFECT: improved preparing method, valuable medicinal properties of compounds.
4 cl, 2 tbl, 568 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to compositions eliciting an antilipidemic effect and comprising inhibitor of bile acid transport in jejunum of the general formula (I): and inhibitor of HMG-CoA-reductase. Also, invention relates to a method for carrying out the combined therapy.
EFFECT: improved treatment method, valuable medicinal properties of compositions.
15 cl, 9 tbl, 1401 ex
FIELD: organic chemistry, medicine, pharmacology.
SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):
and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:
wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.
EFFECT: improved preparing methods, valuable medicinal properties of compounds.
22 cl, 1 tbl, 2 sch, 78 ex
FIELD: organic chemistry, pharmaceutical industry, medicine.
SUBSTANCE: invention relates to new derivatives of S-substituted N-1-[(hetero)aryl]alkyl-N'-1-[(hetero)aryl]alkylisothioureas of general formula I
in form of free base and salts with pharmaceutically accepted acids, as well as racemate, individual optical isomers or mixture thereof. In formula R1, R2, R3, R4, Y and Z are as described in specification. Compounds of present invention are capable to potentiate (positively modulate) AMPA/KA glutamate receptors and simultaneously to block transmembrane currents induced by activation of NMDA glutamate receptors. Also disclosed are method for production of said compounds, including optical isomers; pharmaceutical composition; method for investigation of glutamatergic system, and method for Alzheimer's disease, treatment; as well as method for extreme retentiveness of memory by administering of effective amount of claimed compounds.
EFFECT: new pharmaceutically active compounds for Alzheimer's disease treatment.
23 cl, 1 tbl, 11 ex
FIELD: pharmaceutical industry, in particular new bioactive chalcones.
SUBSTANCE: invention relates to new chalcones of formula I
, pharmaceutically acceptable salts or solvates thereof, wherein Ar is optionally substituted C5-C10-carbocycle group or 5- or 6-membered heterocycle group having sulfur atom in cycle, and Ar substituents are selected independently from Cl, Br, F, CN, SCH3 and OR10, wherein R10 is linear or branched C1-C6-hydrocarbon; R is OH or R10; R2 and R3 are independently phenyl, saturated linear or branched C1-C6-hydrocarbon, or R2 and R3 together with carbon atom attached thereto form 5- or 6-membered carbocycle group with the proviso, that in compounds where R is OH and both R2 and R3 are methyl, Ar is not phenyl, 4-chlorophenyl, 4-chlorophenyl, 4-methylphenyl, 2-chlorophenyl, 3,4-dimethoxyphenyl, or 4-methoxyphenyl. Also disclosed are drug component for treatment or prophylaxis of neoplasm and pharmaceutical compositions with antiproliferation effect based on compounds of formula I.
EFFECT: new chalcone derivatives with value bioactive action.
26 cl, 2 tbl, 22 ex
FIELD: organic chemistry.
SUBSTANCE: invention relates to new lipoic acid derivatives of general formula Ia
1, wherein n = 0-4, integer; -X-Y represents -O(CH2)r-, -CO-N(R3)-(CH2)r-, -N(R4)-CO-(CH2)r; -X'-Y' represents -(CH2)r-, -(CH2)r-N(R3)-(CH2)r-, -(CH2)r-CO-N(R3)-(CH2)2-; R3 and R4 are the same or different and represent hydrogen or alkoxycarbonyl; r = 0-4, integer; Ω represents piperazinyl, piperidyl or phenyl. Also disclosed are method for production the claimed derivatives and pharmaceutical composition, containing the same. Compounds are useful as NO-syntase inhibitors and/or reagents mediating redox state of thiol groups.
EFFECT: new lipoic acid derivatives.
7 cl, 17 ex
FIELD: medicine, pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to a pharmaceutical composition used in stomatology in the topical anesthesia. The pharmaceutical composition comprising articaine hydrochloride and epinephrine hydrochloride and accessory substances, such as sodium metabisulfite, sodium chloride and water for injection involves additionally glycine and pH-regulating substance taken in the definite ratio of components. Invention provides preparing the preparation that is stable, non-toxic and doesn't cause allergic response reactions and elicits highly expressed infiltration and conducting anesthetic activity, good tissue tolerance and activity promoting to accelerated wound-healing in the post-operative period.
EFFECT: improved and valuable medicinal properties of composition.
3 cl, 3 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of carboxylic acids of the formula: wherein Y is taken independently in each case among the group comprising C(O), N, CR1, C(R2)(R3), NR5, CH; q means a whole number from 3 to 10; A is taken among the group comprising NR6; E is taken among the group comprising NR7; J is taken among the group comprising O; T is taken among the group comprising (CH2)b wherein b = 0; M is taken among the group comprising C(R9)(R10), (CH2)u wherein u means a whole number from 0 to 3; L is taken among the group comprising NR11 and (CH2)n wherein n means 0; X is taken among the group comprising CO2H, tetrazolyl; W is taken among the group comprising C, CR15 and N; R1, R2, R3 and R15 are taken independently among th group comprising hydrogen atom, halogen atom, hydroxyl, alkyl, alkoxy-group, -CF3, amino-group, -NHC(O)N(C1-C3-alkyl)-C(O)NH-(C1-C3-alkyl), -NHC(O)NH-(C1-C6-alkyl), alkylamino-, alkoxyalkoxy-group, aryl, aryloxy-, arylamino-group, heterocyclyl, heterocyclylalkyl, heterocyclylamino-group wherein heteroatom is taken among N atom or O atom, -NHSO2-(C1-C3-alkyl), aryloxyalkyl; R4 is taken among the group comprising hydrogen atom, aryl, aralkyl, benzofuranyl, dihydrobenzofuranyl, dihydroindenyl, alkyl, benzodioxolyl, dihydrobenzodioxynyl, furyl, naphthyl, quinolinyl, isoquinolinyl, pyridinyl, indolyl, thienyl, biphenyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, pyrimidinyl and carbazolyl. Other values of radicals are given in the claimed invention. Also, invention relates to pharmaceutical composition used for inhibition binding α4β1-integrin in mammal based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for treatment or prophylaxis of diseases associated with α4β1-integrin.
EFFECT: improved method for inhibition, valuable medicinal properties of compounds.
33 cl, 7 tbl, 42 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to benzothiophenes of the general formula (I): wherein R represents phenyl substituted optionally with halogen atom or pyridine-3yl or pyridine-4-yl substituted optionally with lower alkyl, or -NR1R2 wherein R1 and R2 in common with nitrogen atom (N) to which they are added form heterocyclic rings chosen from group consisting of morpholinyl, thiomorpholinyl, piperidinyl or piperazinyl substituted optionally with -(CH2)n-hydroxy-group, lower alkyl or lower alkoxy-group; n means 0, 1 or 2, and to their pharmaceutically acceptable acid-additive salts. Compounds of the formula (I) show high affinity to A2A receptors and can be used for regulation of many aspects of cellular metabolism. Also, invention describes a medicinal agent based on compounds of the formula (I).
EFFECT: valuable biological and medicinal properties of compounds and drug.
13 cl, 15 ex
FIELD: chemistry; pharmacology.
SUBSTANCE: invention refers to new benzofuran and benzothiophen derivatives of general formula I, , wherein X is chosen from O and S; R1 is chosen from H, (C1-C6)alkyl, C(O)(C1-C6) alkyl and benzoyl; R2 is chosen from phenyl optionally substituted with 1 or 2 substitutes, each independently chosen from CN, NO2, (C1-C6)alkyl, (C1-C6)alkoxy, halogen, halogen(C1-C6)alkyl, pyridyl or benzo[1,3]dioxolyl optionally substituted with (C1-C6)alkyl. There are disclosed pharmaceutical composition based on compounds I and method of treatment.
EFFECT: compounds can be used to treat or prevent diseases associated with malignant cell proliferation.
26 cl, 7 tbl, 365 ex
SUBSTANCE: invention relates to a method for synthesis of galantamine hydrobromide, which includes a method of purifying galantamine through precipitation of galantamine hydrobromide from a mixture of alkaloids obtained from Amaryllidaceae plants which contain galantaminem, with subsequent treatment of hydrobromide with an alkali, extraction and crystallisation of galantamine using a solvent of general formula , in which R1 is hydrogen or methyl, and R2 is selected from n-butyl, isobutyl, fluoro-butyl and tert-butyl.
EFFECT: obtained pure galantamine can be used to obtain galantamide hydrobromide suitable for pharmaceutical applicaion using a conventional method.
11 cl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to novel compounds, which possess qualities to estrogen modulators, of general formula (1) or its pharmaceutically acceptable salt, where R1 represents hydrogen atom or (C1-C6)alkyl, -SO2NR7R8, phenyl (C1-C3)alkyl or (C1-C3)alkyl, substituted with 5-8-member heterocyclic radical, containing nitrogen atom; R2 and R3 each independently represents hydrogen atom or hydroxyl, halogen atom or (C1-C6)alkoxy; X represents O, S, SO, SO2 or NR4; R4 represents hydrogen atom or (C1-C6)alkyl, phenyl, phenyl(C1-C3)alkyl, (C1-C3)alkyl, substituted with 5-8-member saturated heterocyclic radical, containing one nitrogen atom, or group -COR7, -CO2R7 or -SO2NR7R8, where phenyl is not substituted or is substituted with at least one substituent, selected from group which includes hydroxyl, halogen atom or phenyl(C1-C3)alkoxy; Y represents direct bond, -(CR10R11)n- or -R10C=CR11-; R7 and R8 each independently represents hydrogen atom or (C1-C6)alkyl group; R10 and R11 each independently represent hydrogen atom or cyano, or group CONR7R8; n equals 1 or 2; A represents (C3-C12)cycloalkyl or phenyl, where phenyl is not substituted or is substituted with at least one substituent, selected from group which includes hydroxyl, halogen atom, (C1-C3)alkyl, (C1-C3)alkoxy; when X represents NR4, Y and R2 together with containing them indazole cycle can also form 1H-pyrano[4,3,2-cd)indazole; on condition that: 1) when X represents O, S or NR4, R1 represents hydrogen atom or (C1-C6)alkyl, and Y stands for direct bond, then A is not optionally substituted phenyl; 2) when X represents O, R1O represents 6-OH or 6-OCH3, Y represents direct bond and A represents cyclopeptyl, then (R2, R3) or (R3, R2) are different from (H, CI) in position 4, 5; 3) when X stands for O, R1O represents 6-OH, R2 and R3 represent H, and Y represents CH=CH, then A is not phenyl or methoxyphenyl; 4) when X represents SO2, A represents phenyl and R1O represents 5-or 6-OCH3, then (R2, R3) or (R3, R2) are different from (H, OCH3) in position 6- or 5-, compound not being one of the following: 3-phenyl-5-(phenylmethoxy)-1H-indazole; n-hydroxy-3-phenylmethyl-7-(n-propyl)-benz[4,5]isoxazole; 3-(4-chlorphenylmethyl)-6-hydroxy-7-(n-propyl)-benz[4,5]isoxazole; 6-hydroxy-3-(2-phenylethyl)-7(n-propyl)-benz[4,5]isoxazole; 3-cyclopropyl-6-hydroxy-3-phenylmethyl-7-(n-propyl)-benz[4,5|isoxazole; 3-cyclohexylmethyl-6-hydroxy-3-phenylmethyl-7-propyl-benz[4,5]isoxazole. Invention also relates to pharmaceutical composition, application and method of prevention and treatment of disease, where modulation of estrogen receptors is required.
EFFECT: obtaining novel compounds, which possess qualities of estrogen receptors modulators.
18 cl, 7 dwg, 8 tbl, 97 ex
SUBSTANCE: invention relates to a method of producing highly pure 4a,5,9,10,11,12-hexahydro-6H-benzofuro[3a,3,2-en]benzazepine, as well as derivatives thereof of formula I and II , produced from racemic bromonarwedine which is debrominated during catalysis with palladium. The invention involves treatment of the reaction mixture, which takes place in the presence of oxygen or peroxides, such that the palladium catalyst is converted to an insoluble, easily separated form. The following reactions take place via reduction of enantiomerically pure narwedine to enantiomerically pure galantamine, which is then alkylated or dealkylated so as to achieve the corresponding substitution in the nitrogen ring atom. Through subsequent purification such as recrystallisation, residual content of palladium lower than 5 ppm is achieved, which enables direct use as pharmaceutical raw material.
EFFECT: improved method.
6 cl, 4 tbl
SUBSTANCE: invention relates to azoloazine salts of compounds of a fluoroquinolone line of formulae 4a-c , 5a-c , 7a-b and 8a-b , possessing antibacterial and antiviral properties. The claimed compounds can be applied for the creation of a medication for the emergency prevention and treatment of infections, caused by pathogens of both the bacterial and viral origin, including especially dangerous ones. In general formulae 4 and 5 R=CH3, R1=C2H5; R=H, R1=C2H5; R=C2H5, R1=cyclo-C3H7, in formulae 7 and 8 R=H (7a, 8a); R=CH3 (7b, 8b).
EFFECT: increased efficiency of the compound application.
8 tbl, 2 ex